CN115485281B - 一种fgfr及其突变抑制剂,其制备方法和应用 - Google Patents
一种fgfr及其突变抑制剂,其制备方法和应用 Download PDFInfo
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- CN115485281B CN115485281B CN202180032537.4A CN202180032537A CN115485281B CN 115485281 B CN115485281 B CN 115485281B CN 202180032537 A CN202180032537 A CN 202180032537A CN 115485281 B CN115485281 B CN 115485281B
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- alkyl
- substituted
- deuterium
- membered
- cycloalkyl
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- 125000002541 furyl group Chemical group 0.000 description 1
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- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
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- 238000000338 in vitro Methods 0.000 description 1
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- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
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- 239000011630 iodine Substances 0.000 description 1
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- SORXVYYPMXPIFD-UHFFFAOYSA-N iron palladium Chemical compound [Fe].[Pd] SORXVYYPMXPIFD-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
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- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
- 229910000080 stannane Inorganic materials 0.000 description 1
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- 238000006467 substitution reaction Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
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- FJVXFVCBMHGHCE-UHFFFAOYSA-N tert-butyl 3-(4-amino-3-iodopyrazolo[3,4-d]pyrimidin-1-yl)azetidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC1N1C2=NC=NC(N)=C2C(I)=N1 FJVXFVCBMHGHCE-UHFFFAOYSA-N 0.000 description 1
- IATNHULUCXZXBR-UHFFFAOYSA-N tert-butyl 3-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2,5-dihydropyrrole-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC=C1C1=CC=C2N1N=CN=C2N IATNHULUCXZXBR-UHFFFAOYSA-N 0.000 description 1
- JZZNLWOVPQUXRF-UHFFFAOYSA-N tert-butyl 3-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC1C1=CC=C2N1N=CN=C2N JZZNLWOVPQUXRF-UHFFFAOYSA-N 0.000 description 1
- XXBDTKYKFFIAEY-UHFFFAOYSA-N tert-butyl 3-methylsulfonyloxyazetidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(OS(C)(=O)=O)C1 XXBDTKYKFFIAEY-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical group C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
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- IAQRGUVFOMOMEM-ONEGZZNKSA-N trans-but-2-ene Chemical compound C\C=C\C IAQRGUVFOMOMEM-ONEGZZNKSA-N 0.000 description 1
- 150000003918 triazines Chemical class 0.000 description 1
- 125000004784 trichloromethoxy group Chemical group ClC(O*)(Cl)Cl 0.000 description 1
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2020108114909 | 2020-08-13 | ||
| CN202010811490 | 2020-08-13 | ||
| PCT/CN2021/112121 WO2022033532A1 (fr) | 2020-08-13 | 2021-08-11 | Fgfr et inhibiteur de mutation de celui-ci, procédé de préparation correspondant et utilisation associée |
Publications (2)
| Publication Number | Publication Date |
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| CN115485281A CN115485281A (zh) | 2022-12-16 |
| CN115485281B true CN115485281B (zh) | 2023-11-21 |
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| Country | Link |
|---|---|
| US (1) | US20230303575A1 (fr) |
| EP (1) | EP4169922A4 (fr) |
| JP (1) | JP2023530768A (fr) |
| KR (1) | KR20230015419A (fr) |
| CN (1) | CN115485281B (fr) |
| AU (1) | AU2021323844B2 (fr) |
| BR (1) | BR112022026386A2 (fr) |
| CA (1) | CA3184247A1 (fr) |
| MX (1) | MX2023000008A (fr) |
| TW (1) | TWI797711B (fr) |
| WO (1) | WO2022033532A1 (fr) |
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| US20230374015A1 (en) * | 2020-06-05 | 2023-11-23 | Kinnate Biopharma Inc. | Inhibitors of fibroblast growth factor receptor kinases |
| CN115785103A (zh) * | 2022-12-28 | 2023-03-14 | 北京康立生医药技术开发有限公司 | 一种治疗胆管癌药物福巴替尼的合成方法 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007087395A2 (fr) * | 2006-01-25 | 2007-08-02 | Osi Pharmaceuticals, Inc. | INHIBITEURS DE mTOR INSATURES |
| CN103958512A (zh) * | 2012-01-19 | 2014-07-30 | 大鹏药品工业株式会社 | 3,5-双取代炔基苯化合物及其盐 |
| CN105461720A (zh) * | 2014-08-08 | 2016-04-06 | 南京圣和药业股份有限公司 | 吗啉类酪氨酸激酶抑制剂 |
| CN109776544A (zh) * | 2017-11-15 | 2019-05-21 | 上海医药工业研究院 | 吡唑并[3,4-d]嘧啶类化合物及其制备方法和用途 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT3023100T (pt) * | 2013-07-18 | 2019-05-29 | Taiho Pharmaceutical Co Ltd | Fármaco antitumoral para administração intermitente de inibidor de fgfr |
| WO2015008844A1 (fr) * | 2013-07-18 | 2015-01-22 | 大鵬薬品工業株式会社 | Agent thérapeutique pour un cancer résistant à un inhibiteur de fgfr |
| CN107344940B (zh) * | 2016-05-06 | 2020-04-21 | 广东东阳光药业有限公司 | Btk抑制剂及其用途 |
| US20230374015A1 (en) * | 2020-06-05 | 2023-11-23 | Kinnate Biopharma Inc. | Inhibitors of fibroblast growth factor receptor kinases |
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2021
- 2021-08-10 TW TW110129491A patent/TWI797711B/zh active
- 2021-08-11 CA CA3184247A patent/CA3184247A1/fr active Pending
- 2021-08-11 US US18/014,095 patent/US20230303575A1/en active Pending
- 2021-08-11 BR BR112022026386A patent/BR112022026386A2/pt unknown
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- 2021-08-11 MX MX2023000008A patent/MX2023000008A/es unknown
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- 2021-08-11 WO PCT/CN2021/112121 patent/WO2022033532A1/fr active Application Filing
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- 2021-08-11 JP JP2022579114A patent/JP2023530768A/ja active Pending
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007087395A2 (fr) * | 2006-01-25 | 2007-08-02 | Osi Pharmaceuticals, Inc. | INHIBITEURS DE mTOR INSATURES |
| CN103958512A (zh) * | 2012-01-19 | 2014-07-30 | 大鹏药品工业株式会社 | 3,5-双取代炔基苯化合物及其盐 |
| CN105461720A (zh) * | 2014-08-08 | 2016-04-06 | 南京圣和药业股份有限公司 | 吗啉类酪氨酸激酶抑制剂 |
| CN109776544A (zh) * | 2017-11-15 | 2019-05-21 | 上海医药工业研究院 | 吡唑并[3,4-d]嘧啶类化合物及其制备方法和用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA3184247A1 (fr) | 2022-02-17 |
| JP2023530768A (ja) | 2023-07-19 |
| KR20230015419A (ko) | 2023-01-31 |
| BR112022026386A2 (pt) | 2023-02-23 |
| AU2021323844A1 (en) | 2023-01-19 |
| EP4169922A1 (fr) | 2023-04-26 |
| MX2023000008A (es) | 2023-01-30 |
| WO2022033532A1 (fr) | 2022-02-17 |
| AU2021323844B2 (en) | 2023-07-27 |
| CN115485281A (zh) | 2022-12-16 |
| US20230303575A1 (en) | 2023-09-28 |
| TW202206433A (zh) | 2022-02-16 |
| EP4169922A4 (fr) | 2024-03-13 |
| TWI797711B (zh) | 2023-04-01 |
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